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ObjectiveMany persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood.Method and participantsStudy participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time.ResultsHPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14.ConclusionsWorsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

ObjectivesUncovering heterogeneities in longitudinal patterns (trajectories) of opioid use among individuals with opioid use disorder can increase our understanding of disease progression and treatment responses to improve care. The present study aims to identify distinctive opioid use trajectories and factors associated with these patterns among participants randomized to treatment with methadone (MET) or buprenorphine + naloxone (BUP).MethodsGrowth mixture modeling was applied to identify distinctive opioid use trajectories among 795 opioid users after their enrollment in a multisite trial during 2006 to 2009, with follow-up interviews conducted during 2011 to 2014.ResultsFour distinctive trajectories were identified based on opioid use over the follow-up period: low use (42.0%), high use (22.3%), increasing use (17.1%), and decreasing use (18.6%). Greater odds of being in the high use group (relative to low use) was associated with Hispanics (relative to African American, odds ratio [OR] 3.21), injection drug use (OR 2.12), higher mental health functioning at baseline (OR 1.23), location on the West Coast (vs East Coast, OR 2.15), and randomization to BUP (relative to MET, OR 1.53). High use and increasing use groups had greater severity in problems related to drug, employment, legal, and social/family relationships, and worsened mental health functioning at follow-up. Participation in treatment significantly accounted for both within and between-group differences in opioid use.ConclusionsContinued treatment is necessary to reduce risk for opioid use and related adverse consequences, particularly among individuals (eg, injecting drug) at risk for consistently high level of opioid use.

AimsTo compare long-term outcomes among participants randomized to buprenorphine or methadone.Design, setting and participantsFollow-up was conducted in 2011-14 of 1080 opioid-dependent participants entering seven opioid treatment programs in the United States between 2006 and 2009 and randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24 weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering on average 4.5 years.MeasurementsOutcomes were indicated by mortality and opioid use. Covariates included demographics, site, cocaine use and treatment experiences.FindingsMortality was not different between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died versus 26 (5.8%) of 450 participants randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone [42.8 versus 31.7% positive opioid urine specimens, P < 0.01, effect size (h) = 0.23 (0.09, 0.38); 5.8 days versus 4.4 days of past 30-day heroin use, P < 0.05, effect size (d) = 0.14 (0.00, 0.28)]. Opioid use during the follow-up period by randomization condition was also significant (F(7,39,600) = 3.16; P < 0.001) due mainly to less treatment participation among participants randomized to buprenorphine than methadone. Less opioid use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference was found between the two treatments. Individuals who are white or used cocaine at baseline responded better to methadone than to buprenorphine.ConclusionsThere are few differences in long-term outcomes between buprenorphine and methadone treatment for opioid dependence, and treatment with each medication is associated with a strong reduction in opioid use.

BackgroundThe development and approval of an efficacious pharmacotherapy for stimulant use disorders has been limited by the lack of a meaningful indicator of treatment success, other than sustained abstinence.MethodsIn March, 2015, a meeting sponsored by Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) was convened to discuss the current state of the evidence regarding meaningful outcome measures in clinical trials for stimulant use disorders. Attendees included members of academia, funding and regulatory agencies, pharmaceutical companies, and healthcare organizations. The goal was to establish a research agenda for the development of a meaningful outcome measure that may be used as an endpoint in clinical trials for stimulant use disorders.Results and conclusionsBased on guidelines for the selection of clinical trial endpoints, the lessons learned from prior addiction clinical trials, and the process that led to identification of a meaningful indicator of treatment success for alcohol use disorders, several recommendations for future research were generated. These include a focus on the validation of patient reported outcome measures of functioning, the exploration of patterns of stimulant abstinence that may be associated with physical and/or psychosocial benefits, the role of urine testing for validating self-reported measures of stimulant abstinence, and the operational definitions for reduction-based measures in terms of frequency rather than quantity of stimulant use. These recommendations may be useful for secondary analyses of clinical trial data, and in the design of future clinical trials that may help establish a meaningful indicator of treatment success.

Over the past decade, the amount and variety of addiction research around the world has increased substantially. Researchers in Australia, Canada, United Kingdom, United States, and western Europe have significantly contributed to knowledge about addiction and its treatment. However, the nature and context of substance use disorders and the populations using drugs are far more diverse than is reflected in studies done in Western cultures. To stimulate new research from a diverse set of cultural perspectives, the National Institute on Drug Abuse (NIDA) has promoted the development of addiction research capacity and skills around the world for over 25 years. This review will describe the programs NIDA has developed to sponsor international research and research fellows and will provide some examples of the work NIDA has supported. NIDA fellowships have allowed 496 individuals from 96 countries to be trained in addiction research. The United Arab Emirates and Saudi Arabia have recently developed funding to support addiction research to study, with advice from NIDA, the substance use disorder problems that affect their societies. Examples from Malaysia, Tanzania, Brazil, Russian Federation, Ukraine, Republic of Georgia, Iceland, China, and Vietnam are used to illustrate research being conducted with NIDA support. Health services research, collaboratively funded by the U.S. National Institutes of Health and Department of State, addresses a range of addiction service development questions in low- and middle-income countries. Findings have expanded the understanding of addiction and its treatment, and are enhancing the ability of practitioners and policy makers to address substance use disorders.

ObjectivesCompare HIV injecting and sex risk in patients being treated with methadone (MET) or buprenorphine-naloxone (BUP).MethodsSecondary analysis from a study of liver enzyme changes in patients randomized to MET or BUP who completed 24 weeks of treatment and had 4 or more blood draws. The initial 1:1 randomization was changed to 2:1 (BUP:MET) after 18 months due to higher dropout in BUP. The Risk Behavior Survey measured HIV risk before 30 days at baseline and weeks 12 and 24.ResultsAmong 529 patients randomized to MET, 391 (74%) were completers; among 740 randomized to BUP, 340 (46%) were completers; 700 completed the Risk Behavior Survey. There were significant reductions in injecting risk (P < 0.0008) with no differences between groups in mean number of times reported injecting heroin, speedball, other opiates, and number of injections; or percent who shared needles; did not clean shared needles with bleach; shared cookers; or engaged in front/back loading of syringes. The percent having multiple sex partners decreased equally in both groups (P < 0.03). For males on BUP, the sex risk composite increased; for males on MET, the sex risk decreased resulting in significant group differences over time (P < 0.03). For females, there was a significant reduction in sex risk (P < 0.02) with no group differences.ConclusionsAmong MET and BUP patients who remained in treatment, HIV injecting risk was equally and markedly reduced; however, MET retained more patients. Sex risk was equally and significantly reduced among females in both treatment conditions, but it increased for males on BUP and decreased for males on MET.

Among agents for treatment of opioid addiction, methadone is a full mu-opioid receptor agonist, whereas buprenorphine is a partial agonist. Both are long-acting. Buprenorphine has a superior safety profile. Methadone is formulated for oral administration and buprenorphine for sublingual administration. A subdermal buprenorphine implant with a 6-month duration of action is being considered for approval by the U.S. Food and Drug Administration. Both medications reduce mortality rates and improve other outcomes. Data from a recent randomized controlled comparison of both medications (N = 1269) show better treatment retention with methadone but reduced illicit opioid use early in treatment with buprenorphine. Human immunodeficiency virus (HIV) risk behaviors were measured using the Risk Behavior Survey at baseline, 12 weeks, and 24 weeks for study completers. In the 30 days prior to treatment entry, 14.4% of the completers randomized to treatment with buprenorphine (n = 340) and 14.1% of the completers randomized to methadone treatment (n = 391) shared needles. The percent sharing needles decreased to 2.4% for buprenorphine and 4.8 for methadone in the 30 days prior to Week 24 (p < 0.0001). In the 30 days prior to treatment entry, 6.8% of the completers randomized to buprenorphine and 8.2% of the completers randomized to methadone had multiple sexual partners, with only 5.2% and 5.1%, respectively, reporting multiple partners at Week 24 (p < 0.04).

Background/objectivesHIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV activities of the CTN during its first 10 years.ResultsWhile emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs.Conclusion/significanceWhile the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed.